We have:(a) successfully disrupted uteroglobin (UG) gene in mice by homologous recombination and obtained germline transmission in F1 progeny; (b) developed an animal model expressing UG-antisense mRNA at high copy number; (c) cloned and characetrized the entire human UG gene; (d) delineated that UG gene expression in the rabbit uterus and in fetal lung occurs throughout gestation and that in the uterus this gene expression dramatically declines just prior to parturition, suggesting an important physiological role for this protein; (e) established and characterized two temperature-sensitive epithelial cell lines derived from the rabbit trachea and alveoli which differentiate in vitro and express UG and osteopontin genes;(f) resolved the crystallographic structure of recombinant hUG at 2.1 angstroms resolution; (g) resolved the solution structure of recombinant hUG by multidimensional NMR and CD; the results suggest that this protein is nearly identical to rabbit UG; (h) discovered that hUG inhibits cellular invasion via a novel high- affinity cell surface binding protein on NIH 3T3 and human trophoblast cells and human choriocarcinoma cells appear to lack this receptor and consequently, their invasiveness is not reduced by hUG; (i) demonstrated that hUG transcriptionally downregulate cyclooxygenase I & II via its receptor; (j) developed a mouse model which expresses osteopontin (OPN) antisense mRNA at high level; (k) determined that group I PLA2-induced arachidonic acid release from NIH 3T3 cells may be receptor mediated; (l) demonstrated that group I PLA2 can induce cellular invasion via its high- affinity receptor; (m) using both in vitro as well as in vivo assays demonstrated that cells lacking proto-oncogene c-src fail to express OPN gene; since OPN is required for normal osteoclast attachment to the osteoid, a process essential for bone remodeling, our results, at least in part, explains why c-src-/- mice would develop osteopetrosis and (n) delineated that there is an intrinsic abnormality in epithelial cells derived from cystic fibrosis patients carrying delta F508 mutation in cystic fibrosis gene, raising the possibility that novel strategies to control inflammation in the airway of these patients may include inhibition of PLA2 activity.